Neuraminidase inhibitors for preventing and treating influenza in healthy adults: systematic review and meta-analysis

Objective: To update a 2005 Cochrane review that assessed the effects of neuraminidase inhibitors in preventing or ameliorating the symptoms of influenza, the transmission of influenza, and complications from influenza in healthy adults, and to estimate the frequency of adverse effects. Search strategy: An updated search of the Cochrane central register of controlled trials (Cochrane Library 2009, issue 2), which contains the Acute Respiratory Infections Group’s specialised register, Medline (1950-Aug 2009), Embase (1980-Aug 2009), and post-marketing pharmacovigilance data and comparative safety cohorts. Selection criteria: Randomised placebo controlled studies of neuraminidase inhibitors in otherwise healthy adults exposed to naturally occurring influenza. Main outcome measures: Duration and incidence of symptoms; incidence of lower respiratory tract infections, or their proxies; and adverse events. Data extraction: Two reviewers applied inclusion criteria, assessed trial quality, and extracted data. Data analysis: Comparisons were structured into prophylaxis, treatment, and adverse events, with further subdivision by outcome and dose. Results: 20 trials were included: four on prophylaxis, 12 on treatment, and four on postexposure prophylaxis. For prophylaxis, neuraminidase inhibitors had no effect against influenza-like illness or asymptomatic influenza. The efficacy of oral oseltamivir against symptomatic laboratory confirmed influenza was 61% (risk ratio 0.39, 95% confidence interval 0.18 to 0.85) at 75 mg daily and 73% (0.27, 0.11 to 0.67) at 150 mg daily. Inhaled zanamivir 10 mg daily was 62% efficacious (0.38, 0.17 to 0.85). Oseltamivir for postexposure prophylaxis had an efficacy of 58% (95% confidence interval 15% to 79%) and 84% (49% to 95%) in two trials of households. Zanamivir performed similarly. The hazard ratios for time to alleviation of influenza-like illness symptoms were in favour of treatment: 1.20 (95% confidence interval 1.06 to 1.35) for oseltamivir and 1.24 (1.13 to 1.36) for zanamivir. Eight unpublished studies on complications were ineligible and therefore excluded. The remaining evidence suggests oseltamivir did not reduce influenza related lower respiratory tract complications (risk ratio 0.55, 95% confidence interval 0.22 to 1.35). From trial evidence, oseltamivir induced nausea (odds ratio 1.79, 95% confidence interval 1.10 to 2.93). Evidence of rarer adverse events from pharmacovigilance was of poor quality or possibly under-reported. Conclusion: Neuraminidase inhibitors have modest effectiveness against the symptoms of influenza in otherwise healthy adults. The drugs are effective postexposure against laboratory confirmed influenza, but this is a small component of influenza-like illness, so for this outcome neuraminidase inhibitors are not effective. Neuraminidase inhibitors might be regarded as optional for reducing the symptoms of seasonal influenza. Paucity of good data has undermined previous findings for oseltamivir’s prevention of complications from influenza. Independent randomised trials to resolve these uncertainties are needed

Study of contemporary medical politics

Thesis (Ph. D. in History, Anthropology, and Science, Technology and Society (HASTS))--Massachusetts Institute of Technology, Program in Science, Technology and Society, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 271-312).Over the past decade, the prevention and control of seasonal and pandemic influenza has grown to be one of the largest and most visible public health policies. This dissertation considers contemporary influenza policy as a case study in what I call medical politics, in which a disease that for most people is rather unremarkable has become the focus of intense (and costly) public health campaigns based on a shaky scientific basis. The dissertation seeks to explain how this could happen. The first two chapters show how influenza and its pandemics are marketed through an appeal to numerous scientific claims. Drawing on governmental marketing materials, statements by officials, and policy documents, I try to let officials speak for themselves and, as much as possible, refrain from analysis. Chapter 3 tells the story of the 2009 novel influenza H1N1 outbreak, showing how official understandings about influenza were called into question by an outbreak far milder than experts had predicted, and discusses investigations which highlighted the role of industry in shaping influenza policy. Chapter 4 analyzes official scientific claims regarding influenza, and argues that degree to which influenza is a serious public health problem is actually unclear. Furthermore, influenza vaccine effectiveness has been vastly overstated, predictive models of pandemic influenza are demonstrably flawed, and officials conflate true influenza with influenza-like illness (ILl), an often overlooked but critical distinction which allows officials to mislead the public into holding false assumptions about the potential benefits of influenza vaccine. Chapter 5 highlights the centrality of "virus-centric thinking" and the ethic of "saving lives" in public health practice as important factors that help explain how such a situation can exist and persist in light of the evidence. Chapter 6 addresses the policy implications of the dissertation's findings.by Peter N. Doshi.Ph.D.in History, Anthropology, and Science, Technology and Society (HAST

In vitro antifungal effect of mouth rinses containing chlorhexidine and thymol

AbstractBackground/purposeIn this in vitro study, we assessed the antifungal effect of mouth rinses containing chlorhexidine and thymol.Materials and methodsThe fungistatic activities of chlorhexidine- and thymol-containing mouth rinses were assessed by means of the minimum inhibitory concentration (MIC) and the fungicidal activity was determined by a time-kill assay.ResultsThe chlorhexidine-containing mouthwash was able to kill all strains of Candida albicans and Candida tropicalis in shorter times compared to the thymol-containing mouthwash. Hexidine showed an MIC of 1:32 for both Candida species, whereas Listerine respectively showed MICs of 1:8 and 1:16 for C. albicans and C. tropicalis.ConclusionsAntimicrobial agents used in the study had good in vitro activity against the two Candida species. Mouth rinses containing chlorhexidine showed superior antifungal and fungicidal activities compared to the thymol-containing mouth rinse. Both antimicrobial agents may be suggested for use as topical antifungal agents

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

Transparency Too Little, Too Late? Why and How Health Canada Should Make Clinical Data and Regulatory Decision-Making Open to Scrutiny in the Face of COVID-19

Hard-won gains in the transparency of therapeutic product data in recent years1 have occurred alongside growing reliance by regulators upon expedited review processes.2 The concurrence of these two trends raises fundamental questions for the future of pharmaceutical regulation about whether the institutionalization of transparency will foster improved oversight of drugs, biologics, vaccines, and other interventions, or else, provide cover for a relaxing of regulatory standards of safety, effectiveness, and quality.3 The urgency of the COVID-19 pandemic, however, has brought this tension into immediate and sharp relief. During the course of the global health crisis, regulatory bodies have markedly expanded the number and use of expedited review processes for COVID-19 therapies, and at the same time, the proliferation of misinformation about any potential SARS-CoV-2 intervention4 reveals the limitations of recently implemented transparency measures

Baseload Fission Reactor for Lunar Operations

Breakout performance for human operations will be realized once there are MW-class continuousoperation fission reactors on the Moon. This is likely to be realized only when there is a means for producing fissile fuel from ISRU resources, such as lunar thorium, because of the concerns associated with earth-launch of radioactive materials. Space is pervaded by gamma rays which produce neutrons upon interaction with beryllium. When moderated by graphite said neutrons can be captured by the thorium nucleus, which transmutes into protactinium, which further decays into the U-233 isotope of uranium. U233 is an excellent source because the radioactive byproducts of spent fuel are short-lived, becoming safe after about 80 years. Thorium dioxide (ThO2 or thoria) is much more dense than the regolith average, and is found in concentrations exceeding those on earth in certain craters of the north Near Side, possibly because of the excavation of rich subsurface deposits due to meteorite impacts. Using jaw crushers and trommels made of durable lightweight metals a lunar mining operation can extract hundreds of kilograms of thoria by using a polymeric adaptation of a Wilfley sorting table laid along the sloped wall of a crater. An acid leach process can be used to remove intermediate protactinium from further neutron irradiation, which will decay to U-233. After processing the transmutated urania (UO2) is packed into fuel rods for a first-generation lunar fission reactor. The same gamma rays and beryllium will initiate a controlled chain reaction to provide baseload power. A Brayton cycle generator can produce power in a manner similar to the small modular reactor concept in development for terrestrial loads. With power outputs in the range of 10 to 60 MW, a single reactor can provide heat and power for a sizeable human base plus mining operations, as well as electromagnetic launchers to deliver payloads into orbit. Water harvested from polar craters can be shipped to any orbit. Greenhouses on the Moon can become the breadbasket to the Solar System. Electric power can be delivered over transmission lines, or via wireless power transfer to a variety of loads such as rovers, orbiting spacecraft, and even multiple habitats. With no nuclear materials needing to be launched from the earth’s surface, and with relatively short-lived hot waste, this is a pathway to the long duration settlement of the Moon